It has been established during the past fifteen years that glycosphingolipids have immunological properties and function as immunological determinants in cell membranes. One of these, cytolipin H, having only two carbohydrate residues, is associated with human malignant tissue in the following way: when antisera are produced in rabbits against many types of human malignant tissue, they frequently contain antibodies against cytolipin H. This is not true of normal human tissues or either normal or malignant animal tissues. Since cytolipin H is one of the weakest glycosphingolipids immunogenically and is also a fundamental part of the structure of most of the more complex glycosphingolipids (which are biosynthesized by sequential addition of carbohydrate residues in normal tissues), the observations suggest that cytolipin H is a significant indicator of some abnormality in the membrane structure of human malignant cells. This abnormality may be expressed either as a deficiency in the more complex glycosphingolipids or as an excessive quantity of cytolipin H. The proposed studies are designed to establish the basis for the observed induction of antibodies to cytolipin H on immunization with human tumors, to determine whether cytolipin H does reflect abnormal membrane structure, and to develop further the immunochemistry of glycosphingolipids as markers of alterations in cells during transformation or abnormal development.